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Pharmacol Rep. 2014 Jun;66(3):471-9. doi: 10.1016/j.pharep.2013.08.015. Epub 2014 Mar 6.

A novel synthetic HTB derivative, BECT inhibits lipopolysaccharide-mediated inflammatory response by suppressing the p38 MAPK/JNK and NF-κB activation pathways.

Author information

1
Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea.
2
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Republic of Korea.
3
Department of Biotechnology, Research Institute for Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea. Electronic address: choidk@kku.ac.kr.

Abstract

Activated microglia cells are well recognized as mediators of neuroinflammation, as they release nitric oxide and pro-inflammatory cytokines in various neuroinflammatory diseases. Thus, suppressing microglial activation may alleviate neuroinflammatory and neurodegenerative processes. In the present study, we synthesized and investigated the anti-neuroinflammatory effect of a novel HTB (2-hydroxy-4-trifuoromethylbenzoic acid) derivative in lipopolysaccharide (LPS)-stimulated microglial cells. Among the synthesized derivatives, the BECT [But-2-enedioic acid bis-(2-carboxy-5-trifluoromethyl-phenyl) ester] significantly decreased production of nitric oxide and other pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in microglial cells. BECT also mitigated the expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. Further mechanistic studies demonstrated that the HTB derivative inhibited phosphorylation of JNK and p38 mitogen-activated protein kinase and nuclear translocation of nuclear factor kappa-B in LPS-stimulated BV-2 microglial cells. Thus BECT, our novel synthesized compound have anti-inflammatory activity in microglial cells, and may have therapeutic potential for treating neuroinflammatory diseases.

KEYWORDS:

HTB derivative; Lipopolysaccharide; Microglia; Neurodegenerative disease; Neuroinflammation

PMID:
24905526
DOI:
10.1016/j.pharep.2013.08.015
[Indexed for MEDLINE]
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